The goals of the 39 members of the Developmental Therapeutics and Clinical Trials Program are to conduct laboratory studies that identify strategies for new and more effective therapy for cancer and then to test those strategies in clinical trials. Our specific aims are to improve treatment: 1) by gaining a better understanding of mechanisms of drug cytotoxicity and resistance; 2) by identify drugs that activate new cellular pathways of cytotoxicity; 3) by development complementary modes of treatment, including and radiation; and 4) by conducting phase I and II clinical trials that include pharmacokinetics and pharmacodynamics as well as measures of response using cellular and molecular surrogates and functional imaging. The Program encompasses laboratory development of new therapeutic strategies for solid tumors and leukemia and clinical therapeutic studies. Major areas of research are novel and conventional chemotherapy, which includes alkylating agents, platinum compounds, topoisomerase inhibitors, anti-metabolites, retinoids, and photosensitizers; immunotherapy, which includes peptide vaccines, peptide pulsed dendritic cells, and DNA-based vaccines as well as humanized monoclonal antibodies and monoclonal antibody/cytokine fusion proteins; anti-angiogenesis therapy targeting endothelial cell integrins, matrix metalloproteinases, and proteolyzed collagen; and gene therapy, which modifies leukemia cells rendering them more immunogenic and which targets retroviral vectors to tumors and tumor vasculature. Considerable efforts are focusing on developing strategies for treating minimal residual disease with retinoids, immunotherapy, and anti-angiogenesis therapies that are not affected by mechanisms by which cancer cells become resistant to chemotherapy and irradiation. Preclinical basic and translational laboratory studies are (CHLA) Research Institute. Phase I and II studies are conducted at the USC/Norris Comprehensive Cancer Center Hospital, USC/LA County Hospital, and CHLA, and promising studies are expanded throughout the country as consortium and cooperative group studiers. The Program is supported by $6.6 million in total direct costs.